Specificity of Cancer-related Chromosomal Translocations is Linked to Proximity After the DNA Double-strand Break and Subsequent Selection

Overview

Journal NAR Cancer

Publisher Oxford University Press

Specialty Oncology

Date 2023 Sep 26

PMID 37750169

Authors

Reynand Jay Canoy

Anna Shmakova

Anna Karpukhina

Nikolai Lomov

Eugenia Tiukacheva

Yana Kozhevnikova

Franck Andre

Diego Germini

Yegor Vassetzky

Affiliations

Soon will be listed here.

Abstract

Most cancer-related chromosomal translocations appear to be cell type specific. It is currently unknown why different chromosomal translocations occur in different cells. This can be due to either the occurrence of particular translocations in specific cell types or adaptive survival advantage conferred by translocations only in specific cells. We experimentally addressed this question by double-strand break (DSB) induction at , , and loci in the same cell to generate chromosomal translocations in different cell lineages. Our results show that any translocation can potentially arise in any cell type. We have analyzed different factors that could affect the frequency of the translocations, and only the spatial proximity between gene loci after the DSB induction correlated with the resulting translocation frequency, supporting the 'breakage-first' model. Furthermore, upon long-term culture of cells with the generated chromosomal translocations, only oncogenic - and - translocations persisted over a 60-day period. Overall, the results suggest that chromosomal translocation can be generated after DSB induction in any type of cell, but whether the cell with the translocation would persist in a cell population depends on the cell type-specific selective survival advantage that the chromosomal translocation confers to the cell.

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